Respiratory syncytial virus infection in immunosuppressed animals: implications in human infection.

Neonatal cotton rats were treated with cyclophosphamide parenterally for three weeks before intranasal inoculation of live respiratory syncytial virus (RSV). Immunosuppressive therapy resulted in severe depletion of lymphocytes from the peripheral circulation, the spleen, and the thymus. In contrast to normal rats, immunosuppressed animals developed severe pulmonary pathology with marked infiltration of foamy macrophages. Persistent degeneration and regeneration of bronchial epithelial cells were also observed, in which RSV antigens could be demonstrated by the immunoperoxidase technique. In addition, large quantities of live virus were recovered from the respiratory tract of these animals for as long as six weeks after infection. Systematic dissemination of RSV, which has never been documented in immunocompetent control rats, was found in four of the cyclophosphamide-treated animals. These results support clinical observations that cellular immunity may be very important in the pathogenesis of RSV infection in the human host.